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Updated: Aug 9, 2025

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Phase separation of Hippo signalling complexes.

Teresa T Bonello1, Danfeng Cai2,3, Georgina C Fletcher4

  • 1EMBL Australia, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.

The EMBO Journal
|February 22, 2023
PubMed
Summary
This summary is machine-generated.

The Hippo pathway

Keywords:
Hippo signallingcondensatesepitheliamechanobiology

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biophysics

Background:

  • The Hippo pathway regulates tissue growth and organ size.
  • Key components include Hippo kinase (Hpo) and Salvador (Sav).
  • Hpo activation typically occurs at the apical domain of epithelial cells.

Purpose of the Study:

  • To investigate the role of biomolecular condensates in Hippo pathway activation.
  • To explore the formation and properties of Hpo-containing complexes.
  • To determine if Hpo condensate formation is conserved across species.

Main Methods:

  • Overexpression of pathway components (Ex, Kib) in Drosophila.
  • Biochemical assays including in vitro phase separation of purified Hpo-Sav complexes.
  • Confocal microscopy to visualize Hpo condensates in Drosophila and human cells.

Main Results:

  • Hpo activation involves the formation of supramolecular complexes with biomolecular condensate properties.
  • Overexpression of Ex or Kib induces cytoplasmic Hpo condensates.
  • Purified Hpo-Sav complexes undergo phase separation in vitro.
  • Hpo condensate formation is conserved in human cells.

Conclusions:

  • Hippo pathway activation is mediated by phase-separated biomolecular condensates.
  • These condensates, termed "signalosomes," form in response to upstream component clustering.
  • This provides a new mechanism for regulating Hpo kinase activity and tissue growth.